Objective of Proposed Research: To continue in close cooperation with my collaborator Dr. Wilbur H. Sawyer, Department of Pharmacology, College of Physicians & Surgeons of Columbia University, New York, N.Y., a joint program aimed at designing, systhesizing and testing for potential clinical application the following: 1) Effective in vivo antagonists of oxytocin for possible use in the prevention of premature deliveries. 2) Antagonists of the antidiuretic response to arginine vasopressin (AVP) for the treatment of hyponatremia resulting from the inappropriate secretion of AVP. 3) Antagonists of the vasopressor response to AVP for use in studies on the possible role of AVP in normal and pathophysiological cardiovascular regulation. 4) Natriuretic/diuretic peptides of potential clinical value. 5) AVP analogs with enhanced pressor/antidiuretic selectivity for possible use in the management of gastrointestinal hemorrhages. The peptides will be synthesized in my laboratory. The pharmacological testing will be carried out in Dr. Sawyer's laboratory. In addition, I hope to meet the following objectives: 6) To further explore the effects of homoserine substitutions at different positions in oxytocin and in AVP on the biological properties of these molecules. 7) To continue to provide other investigators with samples of synthetic peptides for their independent investigations.